Transfer of Lipids from One Compartment to Another

Putative transport/transfer proteins: PC-TP GLTP StAR NPC1

Lipid movement into and out of cells Why do lipids need transporters?

Enterohepatic circulation

Made in ER of intestinal and liver cells Made at surface of cells with appropriate receptors by remodeling VLDLs and chylomicrons

Apoprotein - MW (Da)Lipoprotein AssociationFunction and Comments apoA-I - 29,016Chylomicrons, HDL major protein of HDL, activates lecithin:cholesterol acyltransferase, LCAT apoA-II - 17,400Chylomicrons, HDL primarily in HDL, enhances hepatic lipase activity apoA-IV - 46,000Chylomicrons and HDLpresent in triacylglycerol rich lipoproteins apoB ,000Chylomicrons exclusively found in chylomicrons, derived from apoB-100 gene by RNA editing in intestinal epithelium; lacks the LDL receptor-binding domain of apoB- 100 apoB ,000VLDL, IDL and LDL major protein of LDL, binds to LDL receptor; one of the longest known proteins in humans apoC-I - 7,600 Chylomicrons, VLDL, IDL and HDL may also activate LCAT apoC-II - 8, 916 Chylomicrons, VLDL, IDL and HDL activates lipoprotein lipase

apoC-III - 8,750p Chylomicrons, VLDL, IDL and HDL inhibits lipoprotein lipase apoD, 33,000HDLclosely associated with LCAT cholesterol ester transfer protein, CETPHDL exclusively associated with HDL, cholesteryl ester transfer apoE - 34,000 (at least 3 alleles [E 2, E 3, E 4 ] each of which have multiple isoforms) Chylomicron remnants, VLDL, IDL and HDL binds to LDL receptor, apoE  -4 allele amplification associated with late-onset Alzheimer's disease apoH - 50,000 (also known as  -2- glycoprotein I) Chylomicronstriacylglycerol metabolism apo(a) - at least 19 different alleles; protein ranges in size from 300, ,000 LDL disulfide bonded to apoB-100, forms a complex with LDL identified as lipoprotein(a), Lp(a); strongly resembles plasminogen; may deliver cholesterol to sites of vascular injury, high risk association with premature coronary artery disease and strokelipoprotein(a), Lp(a)

LCAT= lecithin cholesterol acyl tranferase CEPT = cholesteryl-ester transfer protein SR-BI = scavenger receptor, BI So why are LDLs “bad” and HDLs “good”?

The anti-IgG will recognize the half of IgM molecule that does not undergo type switching during maturation. Because antibodies are bivalent, they can cross-link the cell surface immunoglobulins by binding a different cell surface IgM molecule to each of the two antigen binding sites. The cell responds, in turn, by redistributing the cross- linked cell surface immunoglobulins. (a) What are the distribution patterns of IgM on normal and antibody- treated cells. (b) What changes in distribution require metabolic energy from the cell, and what changes occur passively and are due only to the cross-linking. Metabolism is inhibited either by treatment with sodium azide or by incubation at 4oC. By treating cells with fixative before adding the fluorescent antibody, you can determine what the normal, unperturbed immunoglobulin localization is.

control cold hot Hot az Cold azide

Treatment 1 (immediate fixing with fixative): produces ring staining Treatment 2 (no treatment with chemicals; on ice): produces predominantly patching Treatment 3 (sodium azide on ice): produces predominantly patching Treatment 4 (no treatment with chemicals; 37°C): produces capping Treatment 5 (sodium azide at 37°C): produces predominantly patching

Put down that jelly doughnut and look carefully at this aorta. The white arrow denotes the most prominent fatty streak in the photo, but there are other fatty streaks scattered over the aortic surface. Fatty streaks are the earliest lesions seen with atherosclerosis in arteries.

Atherectomy